53IN - Translating genetics into clinical care

Date 27 September 2014
Event ESMO 2014
Session Targeting signalling pathways in haematological malignancies: Are we close to the end of histopathological classification and the chemotherapy era?
Topics Haematologic Malignancies
Personalised Medicine
Translational Research
Presenter Thorsten Zenz
Citation Annals of Oncology (2014) 25 (suppl_4): iv20-iv20. 10.1093/annonc/mdu301
Authors T. Zenz
  • Translational Oncology, NCT/DKFZ/ University Heidelberg, 69120 - Heidelberg/DE

Abstract

Body

Abstract:

Large-scale, world-wide efforts to catalog the genetic, epigenetic, and transcriptional changes that drive human cancers have dramatically increased the known inventory of genes and cellular pathways altered during malignant transformation. These insights provide new therapeutic opportunities, as drugs that interfere with “rewired” pathways will selectively inhibit the viability and proliferation of cancer cells while sparing normal cells. Molecular mechanism-based cancer therapies have, in select instances, led to remarkable therapeutic success (BCR/ABL, BRAFV600E). As a consequence, a multitude of novel approaches targeting critical dependencies of human cancer cells are currently being developed; however, their translation to clinical care is complicated by numerous challenges: In spite of the detailed understanding of genetic changes in lymphoma the immediate impact on clinical care or design of clinical studies remains limited. While high risk genetic lesions are used to explore expedited clinical development, trial activities exploiting molecular understanding are scarce. Administrative burdens and cost hold up trial activity and individual subgroup design. An approach which could speed up trial design could be based on platforms which query sensitivities of molecular subgroups in vitro, to identify disease or molecular subgroup determined sensitivities. Comprehensive studies with primary leukemia material suggest that ex vivo drug response can be extrapolated to predict individual patient outcome. The Wellcome Trust's Genomics of Drug Sensitivity in Cancer (GDSC) project, the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP) have assembled maps of drug sensitivities of hundreds of cell lines, which can be probed for genetically determined drug action. In order to take full advantage of our growing understanding of complex genetic changes in lymphoma, we will have to design trials to allow for adaptive design which may take advantage of the wide armamentarium of drugs and fractionation of molecular subgroups.

Disclosure:

The author has declared no conflicts of interest.